Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.
Specimen part
View SamplesLineage commitment during Embryonic Stem Cells (ESCs) differentiation is controlled not only by a gamut of transcription factors but also by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Moreover, the DNA demethylation agent 5-Aza-2-deoxycytidine (AzadC) has been widely described in the literature as an effective chemical stimulus used to promote cardiomyogenic differentiation in various stem cell types; however, its toxicity and instability complicate its use. Thus, the purpose of this study was to examine the effects of zebularine, a stable and non-toxic DNA cytosine methylation inhibitor, on ESCs differentiation. Herein are the Affymetrix Expression data obtained from RNA of murine ESCs treated with zebularine.
Zebularine regulates early stages of mESC differentiation: effect on cardiac commitment.
Specimen part, Cell line, Treatment
View SamplesWe generated a gene replacement allele of the E-cadherin locus that express an N-cadherin-GFP fusion in ES cells. Expression profiles of homozygous and heterozygous knock-in ES cells were analyzed in comparison to wt ES cells.
Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency.
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View SamplesUnlike human hearts, zebrafish hearts efficiently regenerate after injury. Regeneration is driven by the strong proliferation response of its cardiomyocytes to injury. In this study, we show that active telomerase is required for cardiomyocyte proliferation and full organ recovery, supporting the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction. Overall design: Heart transcriptomes of WT and telomerase defective adult zebrafish animals were profiled by RNASeq, in control conditions and 3 days after heart cryoinjury.
Telomerase Is Essential for Zebrafish Heart Regeneration.
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